DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Claims
Applicant’s amendment filed 07/15/2025 is acknowledged. Claims 23 and 28 have been amended. Claims 1-22 and 24 have been cancelled. Claims 23 and 25-33 are pending in the instant application and the subject of this final office action.
All of the amendments and arguments have been reviewed and considered. Any rejections or objections not reiterated herein have been withdrawn in light of amendments to the claims or as discussed in this office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Previous Rejection
Status of Prior Rejections/Objections:
The claim objections to claim 23 has been withdrawn in view of the amendments to the claim.
The 112(a) rejection to claim 28 is withdrawn in view of the amendments
The prior art rejections under 35 USC 102 directed to claim(s) 23, 25-27, 29-32 as being unpatentable over Fredriksson, as evidenced by MSK and NEB and under 35 USC 103 directed to claim 33 over Fredriksson, as evidenced by MSK and NEB and further in view of Patel are withdrawn in view of the amendments.
New Ground(s) of Rejections
The Applicant's amendment to the claims necessitated the new ground(s) of rejection presented in this Office action.
Drawings
While the drawing were previously accepted in the action on 11/19/2024, the following
objections have since been identified:
Fig. 3 and 4 top panels show the first strand with two 3’ ends. It appears as if the left “3’” were intended to be “5’ ”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 29 is objected to because of the following informalities:
Claim 23 and 29: There is inconsistency in the use of tabs after the letters. Claim 23 (h) and claim 29 (k) – (p) have tabs after the step designator while the others in the respective claims do not.
Claim 29:
In step (k), the claim recites “includes a 5’’ phosphate group”; there is an extra apostrophe after the 5.
In step (n), the claim recites “having a 5’ segment” at the second to third lines of the step. There appears to be an extra line break/tab in the formatting.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
.
Claim(s) 23, 25-32 are rejected under 35 U.S.C. 103 as being unpatentable over Fredriksson (WO 2008/033442 A2; as cited in the IDS dated 02/11/2025; citations below are based on the equivalent US Patent US 8,293,501 B2) in view of Walker (Walker GT, et al. Strand displacement amplification--an isothermal, in vitro DNA amplification technique. Nucleic Acids Res. 1992 Apr 11;20(7):1691-6), as evidenced by MSK (DNA damage recognition and repair by DNA ligases. Memorial Sloan Kettering Institute. Accessed 2024 Nov 12. Available at: https://www.mskcc.org/research/ski/labs/stewart-shuman/dna-damage-recognition-and-repair-dna-ligases), NEB (Reverse Transcription (cDNA synthesis), New England Biolabs. Accessed: 2024 Nov. 13. Available at: https://www.neb.com/en-us/applications/cloning-and-synthetic-biology/dna-preparation/reverse-transcription-cdna-synthesis), and NEB – Ends (What ends will PCR products have? [Internet]. New England Biolabs; 2023 [cited 2025 Oct 11]. Available from: https://www.neb.com/en-us/faqs/2023/07/25/what-ends-will-my-pcr-products-have).
Regarding claims 23, 25, and 29-31, Fredriksson teaches contacting a nucleic acid sample with two or more primer pairs for two or more target nucleic acids under template dependent primer extension reaction conditions, (Abstract; Fig. 2; Fig. 5). Fredriksson teaches that primers have a 3’ target binding portion (Fig. 2). Fredriksson teaches certain ligases require the presence of 5’ end phosphate group to achieve DNA ligation and that one or both primers of a primer pair can be 5’ phosphorylated (col 11, para 2; col 15, lines 1-2).
Fredriksson teaches (col 7, para 1):
In standard PCR reactions known in the art, two primers, often referred to as a forward primer and a reverse primer, work in pairs to generate multiple copies of a specific target nucleic acid sequence present in a nucleic acid sample. In such standard PCR assays, the forward and reverse primers are designed to prime nucleic acid synthesis toward each other on opposite strands of the desired target sequence. By performing repeated cycles of melting, priming; and extending (i.e., nucleic acid synthesis), multiple specific target amplicons are formed. In such standard PCR reactions, the target amplicons formed are double stranded target nucleic acids bounded by the forward and reverse primer sequences
Thus, in teaching the forward and reverse primers are designed to prime nucleic acid synthesis toward each other on opposite strands of the target sequence and performing repeated cycles of melting [i.e., denaturing], priming [i.e., contacting/annealing a target or extended nucleic acid with a first or second primer], and extending [i.e., forming an extended nucleic acid strand] and that one/both primers may be 5’ phosphorylated so as to enable ligation, Fredriksson teaches steps (a)/(i); (b)/j); (c)/(k); (d)/(l); and (e)/(m).
Fredriksson teaches the target amplicons are denatured prior to placing the sample under stringent hybridization conditions to promote strand separation of double stranded amplicons, which allows the circularization template oligonucleotides to anneal to complementary sequences present at the ends of the cognate target amplicons (similar to the annealing in a standard PCR reactions), wherein denaturation (or strand separation) may be carried out by any convenient method (col 9, lines 1-11). Fredriksson teaches hybridizing circularization template oligonucleotides to single-stranded target amplicons (i.e., circularization targets to form circularization complexes (col, 10, para 3; Fig. 3).
Fredriksson that more than one circularization target oligonucleotide may be provided for target amplicons generated by a primer pair (col 12, para 3). Fredriksson further teaches that Taq polymerase is known to sometimes add an additional “A” nucleotide to the 3’ end of an amplified product (this is the reason TA cloning of Taq-amplified targets works), such that two distinct target amplicons are generated when using Taq: those that have an additional “A” and those that don’t (the blunt end amplicon) (col 12, para 3). Fredriksson teaches that to circularize both of these target amplicon species, two circularization oligonucleotides [i.e., bridging oligonucleotides] can be employed, one that will form a circularization complex with the additional “A” target amplicon and one that will form a circularization complex with the blunt end amplicon (col 12, para 3).
Thus, Fredriksson teaches a bridging oligonucleotide that further comprises an additional segment consisting of 1 T nucleotide base between the 5’ and 3’ segments to base-pair with one non-template-determined nucleobase units incorporated in the extended strand to be circularized (instant claim 25) and one without such an additional segment capable of binding to the other extended strand generated by the primer pair, thereby teaching steps (f) and (g)/(n) and (o).
Fredriksson teaches use of any convenient ligating agent such as a DNA ligase, e.g., T4 ligase, to circularize the circularization complex (col 11, para 2; Fig. 2).
Thus, Fredriksson teaches steps (h)/(p).
For steps (e)/(g) and (m)/(o), Fredriksson teaches that the 3’ end of the extended strand has hydroxyl group because Fredriksson teaches ligation of the extended strand (e.g., Fig. 2; Fig. 4; Fig. 5; Fig. 10; col 8, para 3; col 9, para 2, spanning col 10; col 10, para 1), evidenced by MSK. While Fredriksson does not explicitly teach that the extended strand has a 3’ hydroxyl group, it is inherently taught because the ligation reaction requires both a 5’ phosphate and 3’-OH-terminated strand, as evidenced by MSK (DNA Ligase Reaction: “DNA ligases catalyze the joining of a 5’-phosphate-terminated strand to a 3’-hydroxyl-terminated strand…In the third step, ligase catalyzes attack by the 3’-OH … to join the 2 polynucleotides”).
Fredriksson teaches that by multiplex nucleic acid amplification reaction is meant that more than one primer pair specific for a distinct target nucleic acid sequence is included in the reaction, wherein the number of target-specific primer pairs in a multiplex amplification reaction is 2 or more (col 6, para 3; instant claims 30 and 31).
Fredriksson teaches that the multiplex amplification may instead be strand displacement amplification (SDA) instead of PCR (col 7, lines 1-5), but fails to teach specific steps in the SDA such that the denaturing in steps (c) and/or (f) comprises extension of a displacer primer that anneal 3’ of the primers used in bridging.
Walker rectifies this by teaching Strand Displacement Amplification (entire document), comprising a target generation scheme that can be applied techniques separate from SDA as a means of conveniently producing double-stranded fragments with 5’ and 3’ sequences modified as desired (Abstract), including performing PCR reactions with multiple primers and a DNA polymerase possessing strand displacement activity (pg. 1696, col 1, para 4).
Walker teaches that an SDA reaction comprises contacting a target nucleic acid with a first primer having a 3’ target binding segment (e.g., S1) and forming a first extended nucleic acid strand duplexed to the target nucleic acid; displacing [i.e., denaturing] by extending a displacing primer (e.g., B1) that anneals to a position on the target nucleic acid 3’ from the first primer; annealing a 3’ segment of a second primer (e.g., S2) to the first extended strand and forming a second extended nucleic acid duplexed to the first extended strand; and displacing [denaturing] with primer extension of a second displacing primer (e.g., B2) (Fig. 1; pg. 1693, Results, para 2).
Walker teaches that SDA had improved ability to amplify low target numbers at 37 degrees C compared with PCR, which requires the stringency of stringent high temperature reaction conditions (pg. 1695, col 2, para 3). Alternatively, Walker teaches that the target generation scheme using a DNA polymerase with strand displacement ability and the nested primer sets analogous to B1, B2, S1, and S2 should enhance PCR and improve the amount of amplification in early cycles (pg. 1696, col 1, para 3).
Walker teaches that the SDA amplification also results in at least one non-templated 3’ A by teaching that it utilizes an exo- Klenow fragment, evidenced by NEB – Ends. While Walker does not explicitly teach that SDA or the exo- Klenow fragment results in at least one non-templated base, it is inherently taught because the exo- Klenow fragment utilized in Walker (entire document, e.g., Fig. 1 and 2) results in a 3’ A end, evidenced by NEB – Ends (DNA manipulation).
Walker teaches that the steps are performed for both strands at the same time (Figs. 1 and 2; pg. 1692, col 1, SDA Reactions).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the PCR steps of (a)/(i); (b)/j); (c)/(k); (d)/(l); and (e)/(m) in the method of Fredriksson with the target generation steps SDA of Walker, motivated by the desire to be able to amplify low amounts of target molecules, as taught by Walker. Alternatively, it would have been obvious likewise to utilize the displacing primers, as taught by Walker, in the PCR methods of Fredriksson, motivated by the desire to increase the volume of amplification. The use of the bridging oligonucleotide consisting of a T nucleotide of Fredriksson, motivated by the desired capture the species with the non-templated base in Fredriksson, would likewise be obvious to still utilize with Walker’s SDA polymerase in either alternative as it too adds this non-templated base. There would have been a strong expectation of success as both are directed to PCR and SDA amplifications of nucleic acids and this amounts to the application of a known technique to a known method.
Regarding claims 26 and 27, in the method of Fredriksson in view of Walker, as evidenced by MSK, NEB, and NEB – Ends, Fredriksson teaches that the target nucleic acid may be double or single-stranded when contacted with the primers by teaching that the target nucleic acid can be cDNA (col 7, para 3: “the nucleic acid sample can be any of a wide variety [of] types, including… cDNA”), evidenced by NEB. While Fredriksson does not explicitly teach that a target nucleic acid is single stranded, it is inherently taught because “cDNA” may be either single stranded or double stranded, as evidenced by NEB (para. 1: “Reverse transcriptases (RTs) use an RNA template and a short primer complementary to the 3' end of the RNA to direct the synthesis of the first strand cDNA, which can be used directly as a template for the Polymerase Chain Reaction (PCR)…Alternatively, the first-strand cDNA can be made double-stranded using DNA Polymerase I and DNA Ligase.”)
Regarding claim 28, in the method of Fredriksson in view of Walker, as evidenced by MSK, NEB, and NEB – Ends, Walker teaches that primers B1 and B2 can also be SDA primers both target binding regions at their 3’ ends and HincII recognition sites located toward their 5’ ends (pg. 1695, col 2, para 1). Walker teaches that this modification results in an enhancement of amplification from additional nicking an extension/displacement reactions at these outside HincII sites, wherein displaced strands from these outside sites serve as target for both opposite primers (pg. 1695, col 2, para 1).
Walker teaches that the “main” SDA reaction cycle comprises HincII digestion of the extended strand, wherein the portion remaining of the primer 5’ of the digestion site may be considered a “displacer primer” as polymerization and extension displaces the portion of the original extended strand 3’ of the site of digestion in the reaction (Fig. 2).
Walker teaches that single-stranded displaced strand may serve as detector probes (pg. 1695, col 2, para 2).
Thus, interpreting B1 instead as the first primer and the digested B1 5’ fragment as a displacer primer, Walker teaches a modified SDA in which extension of the first primer displaces the complementary strand in duplex with the target nucleic acid (formed by extension of S1) and wherein denaturing in at least step (d) comprises extension of a displacer primer. Utilizing this in the method of Fredriksson as evidenced by MSK and NEB would have been obvious, motivated for the previous reasons and the additional motivation of enhanced amplification, as taught by Walker, and because it would allow for the production of at least two products, such that one could be used for other purposes useful to the artisan such as a detector probe, as taught by Walker. There would have been a strong expectation of success as both are directed to nucleic acid amplifications and this amounts to the application of a known technique to a known method.
Regarding claim 32, in the method of Fredriksson in view of Walker, as evidenced by MSK, NEB, and NEB – Ends, Fredriksson teaches that the circularization template is immobilized on a solid support (col 12, lines 18-19).
Claim(s) 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fredriksson (WO 2008/033442 A2; as cited in the IDS dated 02/11/2025; citations below are based on the equivalent US Patent US 8,293,501 B2) in view of Walker (Walker GT, et al. Strand displacement amplification--an isothermal, in vitro DNA amplification technique. Nucleic Acids Res. 1992 Apr 11;20(7):1691-6), as evidenced by MSK (DNA damage recognition and repair by DNA ligases. Memorial Sloan Kettering Institute. Accessed 2024 Nov 12. Available at: https://www.mskcc.org/research/ski/labs/stewart-shuman/dna-damage-recognition-and-repair-dna-ligases), NEB (Reverse Transcription (cDNA synthesis), New England Biolabs. Accessed: 2024 Nov. 13. Available at: https://www.neb.com/en-us/applications/cloning-and-synthetic-biology/dna-preparation/reverse-transcription-cdna-synthesis), NEB – Ends (What ends will PCR products have? [Internet]. New England Biolabs; 2023 [cited 2025 Oct 11]. Available from: https://www.neb.com/en-us/faqs/2023/07/25/what-ends-will-my-pcr-products-have) as applied to claim 23 above, and further in view of Patel (US 2009/0280538 A1; as cited in the IDS dated 02/15/2022).
Regarding claim 33, in the method of Fredriksson in view of Walker as evidenced by MSK, NEB, and NEB – Ends, Fredriksson teaches that one or more of the target amplicons in a low background amplification reaction of the present invention [i.e., amplifications performed after digesting linear species to remove background; see col 14, para 2] are subjected to nucleic acid sequence analysis, wherein Sanger type sequencing can be performed using one or both of the initial multiplex amplification primers as a sequencing primer(s); pyro-sequencing or other sequencing by synthesis is also applicable (col. 16, para 5). Fredriksson teaches amplification of circular DNA (Fig. 4).
However, Fredriksson fails to teach a sequencing reaction with the generation of a nascent strand using the close nucleic acid structure serving as template.
Patel rectifies this by teaching performing a sequencing reaction serving a template for the generation of a nascent strand from which the sequence of a target nucleic acid is read with the sequencing reaction proceeding around the closed nucleic acid (para [0040]: “Any of the preceding methods of generating closed single stranded nucleic acid loops or single-stranded nucleic acid fragments can further include the step of sequencing the single-stranded nucleic acids, e.g., in a high-throughput sequencing system, such as an array of zero-mode waveguides (ZMWs).”; para [0017]). Patel further teaches that single molecule real-time sequencing (SMRT) is can be used to sequence single-stranded nucleic acid fragments or loops, e.g., produced by any of the methods described herein, in a high-throughput manner, wherein SMRT technology relies on arrays of multiplexed zero-mode waveguides (ZMWs) in which, e.g., thousands of sequencing reactions can take place simultaneously (para [0112]).
Therefore, it would have been obvious to one of ordinary skill in before the time of filing to combine the method of forming a closed nucleic acid structure of Fredriksson in view of Walker, evidenced by MSK, NEB, and NEB – Ends, with the method of sequencing of loops of Patel motivated by the desire to utilize the high-throughput option for sequencing. There would be a strong expectation for success as the artisan is substituting one known sequencing method for another.
Double Patenting
Claims 23 and 25-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. US 10,081,825 B2 in view of Fredriksson (WO 2008/033442 A2; as cited in the IDS dated 02/11/2025; citations below are based on the equivalent US Patent US 8,293,501 B2), Walker (Walker GT, et al. Strand displacement amplification--an isothermal, in vitro DNA amplification technique. Nucleic Acids Res. 1992 Apr 11;20(7):1691-6) and Patel (US 2009/0280538 A1; as cited in the IDS dated 02/15/2022) as evidenced by MSK (DNA damage recognition and repair by DNA ligases. Memorial Sloan Kettering Institute. Accessed 2024 Nov 12. Available at: https://www.mskcc.org/research/ski/labs/stewart-shuman/dna-damage-recognition-and-repair-dna-ligases), NEB (Reverse Transcription (cDNA synthesis), New England Biolabs. Accessed: 2024 Nov. 13. Available at: https://www.neb.com/en-us/applications/cloning-and-synthetic-biology/dna-preparation/reverse-transcription-cdna-synthesis), and NEB – Ends (What ends will PCR products have? [Internet]. New England Biolabs; 2023 [cited 2025 Oct 11]. Available from: https://www.neb.com/en-us/faqs/2023/07/25/what-ends-will-my-pcr-products-have.
Regarding claims 23 and 25, claim 1 of US Pat. ‘825 recites annealing a first primer to a target nucleic acid and extending said first primer to form a first duplex nucleic acid. The claim encompasses an embodiment in which the target nucleic acid is removed to produce a first nucleic acid [instant first extended nucleic acid]. The claim recites annealing a second primer to said first nucleic acid and extended it to produce a second duplex nucleic acid, wherein the claim encompasses the removal of the first nucleic acid to produce a second nucleic acid [instant second extended nucleic acid]. The claim further recites annealing a bridging oligonucleotide to said second nucleic acid where the bridging oligonucleotide has a nucleotide sequence substantially complementary to said second primer and a sequence substantially identical to said first primer, forming a circular second nucleic acid, wherein the 3′-end and 5′-termini of said circular second nucleic acid may be optionally joined by ligase. Claim 2 of US Pat. ‘825 requires recites ligating the second nucleic acid.
While the second primer of US Pat. ‘825 comprises a non-natural nucleotide oligonucleotide at its 5’ end, this is encompassed by the genus claimed in the instant claims. US Pat. ‘825 fails to provide a limiting definition of non-natural nucleotide; therefore, this is interpreted to encompass a synthetically produced primer and the nucleotides used to generate it. And further, should a narrower definition be utilized, it would be prima facie obvious under MPEP 2144.04(II) to exclude the non-natural oligonucleotide from the primer if the function of the non-natural oligonucleotide were not desired (e.g., to raise/lower the Tm and make it more suitable for use with another primer or to avoid the requirement of a modified polymerase tolerant of, for example, nucleotide analogs to generate amplicons from such a template).
While claim 1 of US Pat. ‘825 further recites adding non-natural triphosphates and extending the bridging oligonucleotide to produces an amplicon, it would be prima facie obvious under MPEP 2144.04(II) to exclude the amplification of the circular nucleic acid if a practitioner desired to utilize the circular nucleic acid in another manner (e.g., sequencing the loop itself).
Further, while US Pat. ‘825 does not explicitly teach that the bridging oligonucleotide comprises 1-4 nucleotide bases in an additional segment, the bridging oligonucleotide is recited to be “substantially complementary” to the sequences of the first and second primers. Likewise, Fredriksson, as cited in the 103 rejection above, teaches that a bridging oligonucleotide may comprise 1 T to accommodate a non-templated A added by a Taq polymerase.
Fredriksson further teaches that the low background amplification compositions/methods can improve the accuracy and efficiency of assays and reduce the amount of original nucleic acid sample required without leading to the generation of significant levels of non-target/background amplicons (col 17, para 1).
US. Pat. ‘825 fails to teach that the removing/denaturing comprises extension of a displacer primer in step (c) or (f).
As cited above in the 103 rejection, Walker rectifies this by teaching a method of denaturing utilizing a displacer primer that anneals to a position on the target nucleic acids or a first extended nucleic acid 3’ from a primer.
Walker teaches that these methods are, in part, compatible with PCR and that the enzyme utilized for extension also adds the non-templated bases, as discussed above, evidenced by NEB - Ends.
Walker teaches that SDA has improved ability to amplify low target numbers at certain temperatures and the method can enhance PCR.
As cited above, Fredriksson is also compatible with SDA reactions.
Therefore, it would have been obvious to one of ordinary skill that the bridging oligonucleotide of US Pat. ‘825 may encompass an oligonucleotide with at least one T nucleotide base between the 5’ and 3’ segments in order to allow the practitioner to circularize more nucleic acids when choosing Taq as their polymerase in view of Fredriksson, . There would be a strong expectation of success as designing such a bridging oligonucleotide would require the same techniques as the bridging oligonucleotide of US Pat. ‘825.
Additionally, while US Pat. ‘825 does not explicitly teach that the second primer has a 5’ phosphate group and the second extended strand has a 3’ OH, this is obvious as cited above in view of Fredriksson as evidenced by MSK as US Pat. ‘825 teaches ligation of the second extended strand. Fredriksson, as cited above, teaches that the primers may be phosphorylated to enable ligation with ligases that require it and Fredriksson as evidenced by MSK, as cited above, teaches that OH is required for ligation reactions for such ligases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to utilize phosphorylated primers and that the 3’ end of the extended strand would have had a 3’ OH so that the ligation could proceed without additional steps. There would be a strong expectation of success as obtaining such modified primers utilizes standard molecular biology techniques and/or could be acquired commercially.
Further, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to utilize displacer primers in the method as discussed further in the rejection above at least motivated by the desire to improve the ability to amplify low target numbers at less stringent temperatures and/or enhance amplification of PCR, as taught by Walker.
Regarding claims 26 and 27, in the combined method of claim 23, claim 1 of US Pat. ‘825 recites that the annealing takes place in a mixture comprising a first primer and said target nucleic acid. as cited above, Fredriksson teaches a template nucleic acid may be cDNA, wherein cDNA may be single or double-stranded, as evidenced by NEB. Therefore, it would have been obvious to one of ordinary skill in the art that a contact between a first primer and a target nucleic acid may first occur either a single-stranded or duplexed form, regardless of the duplex status when it is annealed. Providing a target nucleic acid in either a single-stranded or duplex form, depending on the template chosen by the artisan, would enable the artisan to either, for example, save a step in cDNA synthesis or utilize a double-stranded template that is, for example, more resistant to shearing forces. There would be a strong expectation of success as working with both single-stranded and double-stranded templates is well known within the art.
Regarding claim 28, in the combined method of claim 23, Walker teaches the additional SDA cycle steps and the ability to utilize B1 with HincII digestion sites, as discussed in the 103 rejection, wherein utilizing the extension of the first primer to displace the complementary strand from the duplex of S1 would be obvious for the same reasons as above with the same expectations of success.
Response to Arguments
Applicant's arguments filed 07/15/2025 have been fully considered but they are not persuasive.
Regarding the lack of teaching of the use of a displacer primer, as discussed in the new rejection in view of Walker, Fredriksson contemplates SDA as a method for the initial multiplex reaction. Further, while it is acknowledged that Fredriksson teaches stringent hybridization conditions for some embodiments, Fredriksson states that “The initial multiplex PCR is conducted under very non-stringent conditions in order to give all target sequences the best chance of efficient amplification” (col 26, para 1). For at least these reasons and the motivations to combine with Walker discussed in the rejection, the use of displacer primers is found to be both an obvious variant and fully compatible with the methods of Fredriksson.
Applicant’s remaining arguments rely on arguments already addressed above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/EMMA R HOPPE/ Examiner, Art Unit 1683
/Robert T. Crow/ Supervisory Patent Examiner Trainer, Art Unit 4100